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PubMed1984

Beta decay and the origin of biological chirality: new experimental results.

The proposed connection between the parity-violating handedness of beta particles in radioactive decay and the sign (L) of biological chirality (the Vester-Ulbricht [V-U] hypothesis) is being investigated by measuring the theoretically predicted asymmetry in the formation of triplet positronium in amino acid enantiomers by low energy positrons under reversal of the helicity of the positrons. We find the asymmetry in leucine to be (0.8 +/- 1.0) X 10(-4), i.e. consistent with the theoretical prediction of 10(-6) to 10(-7). The apparatus is now sensitive enough to test the predicted asymmetry in optically active molecules which have heavy atoms at their chiral centers. The connection between these results and asymmetry in radiolysis by beta-decay electrons is made, and the implications of our limits for the V-U hypothesis discussed. Although the above limits are 10(6) times lower than direct measurements of radiolysis, they are still not small enough to allow us to rule out the V-U hypothesis.

Elementary Particles↗
PubMed1997

Structure of glycogen particles in organ of Corti's outer hair cells in three rodent species.

Organ of Corti's outer hair cells are one of the few cell types in mammals to contain large cytoplasmic glycogen stores, and the only one in the adult auditory receptor. Previous reports on the structure and distribution of glycogen in the adult organ of Corti were mainly based on light microscopy histo- and cytochemical methods, and the scare EM studies on the topic relied on techniques which were not sensitive or specific enough. Furthermore, it has been reported that glycogen particles are not present in outer hair cells of all species. A first goal of the present study was to describe the ultrastructure of glycogen stores in organ of Corti's outer hair cells in Guinea pig, rat, and mouse, using the periodic acid-thiocarbohydrazide-silver proteinate method. In addition, differences in the subcellular and cochleotopic distribution of this substance were analyzed. In the adult organ of Corti only the outer hair cells contain glycogen stores. Present throughout their cytoplasm, these deposits appear either as single beta particles, or as aggregates of these, forming alpha particles. Though most alpha particles are round, some appear long and conspicuously straight in longitudinal sections of those cells near the apex of the cochlea, and they seem to be apposed to some filamentous structure. On the other hand, when the cells are sectioned transversely the larger aggregates of glycogen particles follow a curved course. Since outer hair cells of the apical region of the cochlea contain a bundle of contractile microfilaments, our results suggest that glycogen is associated with the contractile apparatus of these cells. This hypothesis is in good accordance with previous experimental data which suggest that glycogen is used as energy source for the contractile movements of outer hair cells.

Aging↗
PubMed1998

Reactor-produced radioisotopes from ORNL for bone pain palliation.

The treatment of painful skeletal metastases is a common clinical problem, and the use of therapeutic radionuclides which localize at metastatic sites has been found to be an effective method for treatment of pain, especially for multiple sites for which the use of external beam irradiation is impractical. There are currently several metastatic-targeted agents radiolabeled with various therapeutic radionuclides which are in various stages of clinical investigation. Since neutron-rich radionuclides are produced in research reactors and often decay by emission of beta- particles, most radionuclides used for bone pain palliation are reactor-produced. Key examples of radionuclides produced by single neutron capture of enriched targets include rhenium-186 and samarium-153. In addition, generator systems are also of interest which provide therapeutic daughter radionuclides from the decay of reactor-produced parent radionuclides. One important example is rhenium-188, available from generators via decay of reactor-produced tungsten-188. Tin-117m is an example of a reactor-produced radionuclide which decays with the emission of low-energy conversion electrons rather than by beta- decay. Each of these agents and/or radionuclides has specific advantages and disadvantages, however, the ideal agent for bone pain palliation has not yet been identified. The goal of this paper is to briefly review the production and use of several reactor-produced radionuclides for bone pain palliation, and to discuss the role of the ORNL High Flux Isotope Reactor (HFIR) for the production of many of these radionuclides.

Bone Neoplasms↗
PubMed2001

Effect of stent on radiation dosimetry in an in-stent restenosis model.

Purpose: Intravascular brachytherapy is the leading modality being evaluated for treatment of in-stent restenosis. Stent struts may have an effect on the dose distributions of various radiation sources. We evaluated dosimetry in a stented coronary artery model using a variety of beta and gamma sources and stent materials.Methods: We determined the dose distributions with and without stent in the in-stent restenosis model. Three beta-particle emitting radionuclides, 90Y (2.3 MeV), 144Pr (3.0 MeV), and 106Rh (3.5 MeV), and two gamma-ray emitters, 192Ir (380 keV) and 125I (30 keV), were studied. Stent materials included stainless steel, nitinol, and tantalum. Monte Carlo dose calculations were performed in a stent model of multiple stent struts placed at 1.5 mm from the source. Isodose curves were generated and the ratios of dose rates with and without stent, the stent factors, were evaluated. A stent factor of greater or less than unity represents dose enhancement or reduction in the presence of a stent.Results: For the three beta radionuclides, dose reduction was found on the adventitial side of the stent strut and dose enhancement was noted on the luminal side. On the luminal side, the maximum dose enhancement ranges from 7% to 29%, and the dose reduction on the adventitial side ranges from 13% to 43%. Both the reduction and enhancement effects were most pronounced for the high atomic number material, tantalum. For a given stent material, the dose reduction and enhancement are similar for the three beta radionuclides. For the gamma sources, the stent had no effect for the high-energy 192Ir, but for the low-energy 125I, drastic dose reduction on the adventitial side was observed (up to 86% for tantalum stent), and about 10% dose enhancement on the luminal side was also noted. The dose reduction with 125I was more pronounced than that seen with the beta sources.Conclusions: The presence of stent struts significantly affects dose distributions of 90Y, 106Rh, 144Pr, and 125I. The maximum dose reduction can be as much as 86%. 192Ir was unaffected. These factors need to be considered in choosing radionuclides and dose prescriptions in treating in-stent restenosis.

Journal Article↗
PubMedDate not supplied

Effect of stent on radiation dosimetry in an in-stent restenosis model.

PURPOSE: Intravascular brachytherapy is the leading modality being evaluated for treatment of in-stent restenosis. Stent struts may have an effect on the dose distributions of various radiation sources. We evaluated dosimetry in a stented coronary artery model using a variety of beta and gamma sources and stent materials. METHODS: We determined the dose distributions with and without stent in the in-stent restenosis model. Three beta-particle emitting radionuclides, 90Y (2.3 MeV), 144Pr (3.0 MeV), and 106Rh (3.5 MeV), and two gamma-ray emitters, 192Ir (380 keV) and 125I (30 keV), were studied. Stent materials included stainless steel, nitinol, and tantalum. Monte Carlo dose calculations were performed in a stent model of multiple stent struts placed at 1.5 mm from the source. Isodose curves were generated and the ratios of dose rates with and without stent, the stent factors, were evaluated. A stent factor of greater or less than unity represents dose enhancement or reduction in the presence of a stent. RESULTS: For the three beta radionuclides, dose reduction was found on the adventitial side of the stent strut and dose enhancement was noted on the luminal side. On the luminal side, the maximum dose enhancement ranges from 7% to 29%, and the dose reduction on the adventitial side ranges from 13% to 43%. Both the reduction and enhancement effects were most pronounced for the high atomic number material, tantalum. For a given stent material, the dose reduction and enhancement are similar for the three beta radionuclides. For the gamma sources, the stent had no effect for the high-energy 192Ir, but for the low-energy 125I, drastic dose reduction on the adventitial side was observed (up to 86% for tantalum stent), and about 10% dose enhancement on the luminal side was also noted. The dose reduction with 125I was more pronounced than that seen with the beta sources. CONCLUSIONS: The presence of stent struts significantly affects dose distributions of 90Y, 106Rh, 144Pr, and 125I. The maximum dose reduction can be as much as 86%. 192Ir was unaffected. These factors need to be considered in choosing radionuclides and dose prescriptions in treating in-stent restenosis.

Brachytherapy↗
PubMed1995

Comparison of NIST and manufacturer calibrations of 90Sr+90Y ophthalmic applicators.

Since the resumption of the NIST calibration service for 90Sr+90Y beta-particle ophthalmic applicators, 65 sources have been calibrated using the revised technique [C. G. Soares, Med. Phys. 18, 787-793 (1991)]. For 59 of these sources, the manufacturer's calibration results were available for comparison to the NIST calibration results. The 59 sources represent eight different manufacturers, only one of which is still selling new sources. Manufacturer calibration dates range from the present back to 1954. The results of the comparisons are present, broken down by both manufacturer and calibration date; there are interesting and significant trends in both, with average differences of 20% not uncommon. The obsolete unit, "roentgen-equivalent-beta" (reb), in which some of the manufacturer calibrations are expressed, is discussed, and a factor (0.00982 Gy reb-1) for its conversion to absorbed dose is suggested.

Brachytherapy↗
PubMed1990

Biodistribution, pharmacokinetic, and imaging studies with 186Re-labeled NR-LU-10 whole antibody in LS174T colonic tumor-bearing mice.

Biodistribution, pharmacokinetic, and radioimaging studies were performed with 186Re-labeled NR-LU-10 whole antibody in athymic nude mice bearing the LS174T tumor growing either s.c. or in an experimental hepatic metastasis model. NR-LU-10 is an IgG2b murine monoclonal antibody (MAb) that reacts with virtually all human tumors of epithelial origin. NR-BC-1, a IgG2b murine MAb that reacts with normal human B-cell and B malignancies, was used as an isotype-matched control. These MAbs were radiolabeled with 186Re (3.7-day physical half-life; 1.07-MeV beta particle and 137-keV gamma, 9% abundance) by a preformed chelate approach by using the triamide thiolate ligand system. 186Re-labeled NR-LU-10 (50 microCi) was injected into nude mice bearing LS174T tumors growing s.c. Biodistribution studies revealed that the LS174T tumor retained the highest concentration of 186Re-labeled NR-LU-10 (5.3% injected dose/g) at day 6. The tumor:blood ratio ranged from 0.1:1 to 10.8:1 by day 6, the last day of analysis. In contrast the tumor:blood ratio of 186Re-labeled NR-BC-1, the isotype-matched MAb control, was 1:1 on day 6. Pharmacokinetic analysis indicated that the t1/2 beta of NR-LU-10 for blood and other tissues ranged from 21 to 25 h, while the t1/2 beta for the LS174T tumor averaged 52 h. The area under the curve for tumor compared to blood was 2.8- to 5.7-fold higher than the area under the curve for all other tissues and organs. The mean residence time for NR-LU-10 in blood and all other organs ranged from 23 to 26 h, while the mean residence time for NR-LU-10 in the LS174T tumor was 72 h. Scintigraphic images revealed selective uptake of the 186Re-labeled NR-LU-10, but not of the 186Re-labeled NR-BC-1, at the LS174T tumor site. Studies in an experimental model of hepatic metastasis revealed a similar selective pattern of 186Re-labeled NR-LU-10 accumulation. Scintigraphic images of the LS174T tumor growing within the athymic nude mouse liver were obtained. The biodistribution, pharmacokinetic, and scintigraphic image results suggest that 186Re-labeled NR-LU-10 shows promise as a therapeutic agent for gastrointestinal cancer.

Adenocarcinoma↗
PubMed2001

Efficacy of Re-188-labelled sulphur colloid on prolongation of survival time in melanoma-bearing animals.

UNLABELLED: In this study, the effectiveness of a 188Re labeled sulfur colloid with two particle size ranges was used to evaluate the effectiveness of this agent on melanoma tumors in mice in terms of animal lifespan. METHODS: Two separate group of animals were used for investigating biodistribution and survival time. A total of 188 B16F10-melanoma-bearing BDF(1) mice were injected intraperitoneally with 3.7 MBq (0.1mCi)/2mL of radiolabeled sulfur colloid ten days after intraperitoneal inoculation of 5x10(5) B16F10 melanoma cells/2ml. For group 1, 30 mice were sacrificed at 1, 4, 24, 48 and 72 hours for biodistribution studies. In group 2, 158 mice were divided into 9 groups (n=16 approximately 18/groups)each receiving respectively tumor alone, tumor with normal saline, cold colloid or hot colloid with 16, 23, 31, 46, 62, or 124 MBq activity. Each of these colloid groups was further divided into two groups, one receiving smaller particle sizes (<3 microm:80.4 +/-7.2%, colloid 1) and the other receiving larger particle sizes (<3 microm:12.3+/-1.0%, colloid 2). The animals were checked daily until death and their survival recorded. RESULTS: Colloid 2 showed higher accumulation in almost all tissues, the highest accumulation organ was tumor ( approximately 40%), then spleen ( approximately 20%), stomach ( approximately 15%), diaphragm ( approximately 3%), and liver ( approximately 2%). There was a significant increase in survival time with increasing amount of the larger-particle-size colloid. Administered levels of 16-31 MBq/mouse were most efficacious and with higher amounts the survival times decreased significantly below that of the controls. There was a significant difference in the dose-response curves for the two preparations. Protection factors (1/Relative-risk) of nearly 5 were achieved using the larger colloid size, and nearly 30 using the smaller colloid size. An amount of 16-31 MBq of the colloid 2 was the optimal activity in these studies. On the one hand, the survival data agreed well with the biodistribution data, where higher accumulation was found in tumor with colloid 2. CONCLUSION: Rhenium-188 offers on-site availability, medium half-life, higher beta-particle energy of 2.12 MeV for therapy and emission of 155keV gamma photon suitable for imaging. The present study demonstrated that 188Re-sulfur colloid is an effective agent in controlling tumor cells in the abdominal cavity in animals.

Animals↗
PubMedDate not supplied

Estimation of radiation dose received during treatment of in-stent restenosis using ionizing radiation.

BACKGROUND: Angioplasty is a widely accepted procedure for the treatment of coronary artery disease. However, restenosis of the treated vessel occurs in 30% of patients within 6 months. Intravascular brachytherapy (IVB) is used to inhibit the formation of new tissue growth at the vessel treatment site. IVB protocols using either gamma ray or beta particle emitting isotopes have been tested and approved. However, very little data are available on resultant whole-body dose and the potential for long-term radiation effects. METHODS: Using thermoluminescence dosimetry (TLD) devices, specifically lithium fluoride (LiF) doped with Mg, Cu, and P, the radiation dose on the surface of patients undergoing IVB was measured. The TLDs were positioned on the body to obtain a measure of the gamma dose at selected anatomic locations. Additionally, the skin dose from fluoroscopy was estimated. RESULTS: Measurements indicate that the average body dose on the skin surface from all TLDs, clinical requirements, and gamma source configurations varies from 0.95 mSv (95 mrem) at the head to 27.06 mSv (2706 mrem) at the sternal notch. For beta sources, the dose varied from 0.11 mSv (11.4 mrem) at the head to 0.49 mSv (49.5 mrem) at the sternal notch. The fluoroscopy contribution of dose to the body dose (15-min exposure time) was 0.10 mSv (10 mrem) at the head and 2.57 mSv (257 mrem) to the sternal notch. CONCLUSIONS: The results suggest that surface skin exposures from gamma sources used in IVB pose acceptable risks considering the medical benefits of the procedures.

Brachytherapy↗
PubMed1988

1987 Douglas Lea memorial lecture. Particle dosimetry in bone and the toxicity of bone-seeking radionuclides.

Consideration is given to the tissues at risk in bone and a Monte Carlo method is described which determines the absorbed dose to endosteal tissues and marrow in trabecular bone. The method synthesizes random tracks through the trabecular structures that deposit energy along a path through any given trabecular cavity. The path lengths through the trabeculae and marrow cavities are measured with a bone-scanning microscope and other bone data, such as trabecular surface areas, can also be derived. Results are given for human bones and for bones of the beagle, miniature pig and rhesus monkey. They show that, for the same radionuclide concentration, the doses to endosteal tissues and bone marrow are several times greater in animal than in human bone, and that higher doses in human bone from the Ca and Sr radionuclides are obtained if the initial deposition on bone surfaces is allowed for. Other studies show that the occurrence of osteosarcoma in the human long bones correlates well with trabecular surface area and also that, unlike the case of beta-particles from 90Sr+90Y, leukaemia is not a significant consequence of the alpha-particle doses from 226Ra in human bone or from 226Ra, 239Pu and other alpha emitters in beagle bone.

Bone Neoplasms↗
PubMed1994

Biological effect of lead-212 localized in the nucleus of mammalian cells: role of recoil energy in the radiotoxicity of internal alpha-particle emitters.

The radiochemical dipyrrolidinedithiocarbamato-212Pb(II) [212Pb(PDC)2] is synthesized and its effects on colony formation in cultured Chinese hamster V79 cells are investigated. The cellular uptake, biological retention, subcellular distribution and cytotoxicity of the radiocompound are determined. The 212Pb is taken up quickly by the cells, reaching saturation levels in 1.25 h. When the cells are washed, the intracellular activity is retained with a biological half-life of 11.6 h. Gamma-ray spectroscopy indicates that the 212Pb daughters (212Bi, 212Po and 208Tl) are in secular equilibrium within the cell. About 72% of the cellular activity localizes in the cell nucleus, of which 35% is bound specifically to nuclear DNA. The mean cellular uptake required to achieve 37% survival is 0.35 mBq of 212Pb per cell, which delivers a dose of 1.0 Gy to the cell nucleus when the recoil energy of 212Bi and 212Po decays is ignored and 1.7 Gy when recoil is included. The corresponding RBE values compared to acute external 137Cs gamma rays at 37% survival are 4.0 and 2.3, respectively. The chemical Pb(PDC)2 is not chemotoxic at the concentrations used in this study. Because the beta-particle emitter 212Pb decays to the alpha-particle-emitting daughters 212Bi and 212Po, these studies provide information on the biological effects of alpha-particle decays that occur in the cell nucleus. Our earlier studies with cells of the same cell line using 210Po (emits 5.3 MeV alpha particle) localized predominantly in the cytoplasm resulted in an RBE of 6. These earlier results for 210Po, along with the present results for 212Pb, suggest that the recoil energy associated with the 212Bi and 212Po daughter nuclei plays little or no role in imparting biological damage to critical targets in the cell nucleus.

Alpha Particles↗
PubMed2006

15-Lipoxygenase-mediated modification of high-density lipoproteins impairs SR-BI- and ABCA1-dependent cholesterol efflux from macrophages.

Elevated plasma levels of high-density lipoprotein cholesterol (HDL-C) are atheroprotective and HDL-dependent reverse cholesterol transport has been related to this effect. HDL particles may, however, undergo modifications that affect their biological activities. Lipoxygenases (LOs) belong to a family of lipid peroxidizing enzymes; among them, reticulocyte-type 15-lipoxygenase (15-LO-1) appears to play a pathophysiological role in atherosclerosis, as its expression is increased in atherosclerotic plaques and it has been shown to oxidize low-density lipoproteins to an atherogenic form. In this work we investigated the impact of in vitro 15-lipoxygenase-catalyzed modification of HDL3 on their ability to act as cholesterol acceptor and found that 15-LO-modified HDL3 were less effective in mediating cholesterol efflux from lipid-laden J774 cells. A reduced binding of 15-LO-modified HDL3 to scavenger receptor class B, type I (SR-BI), due to HDL apoproteins cross-linking, explained, at least in part, the observed reduction of cholesterol efflux. In addition, ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux was also reduced, as a consequence of pre-beta-particles loss after HDL3 modification. These results suggest that 15-lipoxygenase might induce structural alterations of HDL3 particles that impair their capability of triggering reverse cholesterol transport.

ATP Binding Cassette Transporter 1↗
PubMed2002

Site-specific variability in trabecular bone dosimetry: considerations of energy loss to cortical bone.

With continual advances in radionuclide therapies, increasing emphasis is being placed on improving the patient specificity of dose estimates to marrow tissues. While much work has been focused on determining patient-specific assessments of radionuclide uptake in the skeleton, few studies have been initiated to explore the individual variability of absorbed fraction data for electron and beta-particle sources in various skeletal sites. The most recent values of radionuclide S values used in clinical medicine continue to utilize a formalism in which electrons are transported under a trabecular bone geometry of infinite extent. No provisions are thus made for the fraction of energy lost to the cortical bone cortex of the skeletal site and its surrounding tissues. In the present study, NMR microscopy was performed on trabecular bone samples taken from the femoral head and humeral proximal epiphysis of three subjects: a 51-year male, an 82-year female, and an 86-year female. Following image segmentation and coupling to EGS4, electrons were transported within macrostructural models of the various skeletal sites that explicitly include the spatial extent of the spongiosa, as well as the thickness of the surrounding cortical bone. These energy-dependent profiles of absorbed fractions to marrow tissues were then compared to transport simulations made within an infinite region of spongiosa. Ratios of mean absorbed fraction, as weighted by the beta energy spectra, under both transport methodologies were then assembled for the radionuclides 32P and 90Y. These ratios indicate that corrections to existing radionuclide S values for 32P can vary by as much as 5% for the male, 6% for the 82-year female, and 8% for the 86-year female. For the higher-energy beta spectrum of 90Y, these same corrections can reach 8%, 10%, and 11%, respectively.

Aged↗
PubMed2003

Monte Carlo dose characterization of a new 90Sr/90Y source with balloon for intravascular brachytherapy.

Beta emitting source wires or seeds have been adopted in clinical practice of intravascular brachytherapy for coronary vessels. Due to the limitation of penetration depth, this type of source is normally not applicable to treat vessels with large diameter, e.g., peripheral vessel. In the effort to extend application of its beta source for peripheral vessels, Novoste has recently developed a new catheter-based system, the Corona 90Sr/90Y system. It is a source train of 6 cm length and is jacketed by a balloon. The existence of the balloon increases the penetration of the beta particles and maintains the source within a location away from the vessel wall. Using the EGSnrc Monte Carlo system, we have calculated the two-dimensional (2-D) dose rate distribution of the Corona system in water for a balloon diameter of 5 mm. The dose rates on the transverse axis obtained in this study are in good agreement with calibration results of the National Institute of Standards and Technology for the same system for balloon diameters of 5 and 8 mm. Features of the 2-D dose field were studied in detail. The dose parameters based on AAPM TG-60 protocol were derived. For a balloon diameter of 5 mm, the dose rate at the reference point (defined as r0 = 4.5 mm, 2 mm from the balloon surface) is found to be 0.01028 Gy min(-1) mCi(-1). A new formalism for a better characterization of this long source is presented. Calculations were also performed for other balloon diameters. The dosimetry for this source is compared with a 192Ir source, commonly used for peripheral arteries. In conclusion, we have performed a detailed dosimetric characterization for a new beta source for peripheral vessels. Our study shows that, from dosimetric point of view, the Corona system can be used for the treatment of an artery with a large diameter, e.g., peripheral vessel.

Brachytherapy↗
PubMed2000

Voxel size effects in three-dimensional nuclear magnetic resonance microscopy performed for trabecular bone dosimetry.

An important problem in internal dosimetry is the assessment of energy deposition by beta particles within trabecular regions of the skeleton. Recent dosimetry methods for trabecular bone are based on Monte Carlo particle transport simulations within three-dimensional (3D) images of real human bone samples. Nuclear magnetic resonance (NMR) microscopy is a 3D imaging technique of choice due to the large signal differential between bone tissue and the water-filled marrow cavities. Image voxel sizes currently used in NMR microscopy are between 50 microm and 100 microm, but the images are time consuming to acquire and can only be performed at present for in vitro samples. It is therefore important to evaluate what resolution is best suitable in order to properly characterize the trabecular microstructure, to adequately predict the tissue dosimetry, and to minimize imaging time. In this work, a mathematical model of trabecular bone, composed of a distribution of spherical marrow cavities, was constructed. The mathematical model was subsequently voxelized with different voxel sizes (16 microm to 1,000 microm) to simulate 3D NMR images. For each image, voxels are assigned to either bone or marrow according to their enclosed marrow fraction. Next, the images are coupled to the EGS4 electron transport code and absorbed fractions to bone and marrow are calculated for a marrow source of monoenergetic electrons. Radionuclide S values are also determined for the voxelized images with results compared to data calculated for the pure mathematical sample. The comparison shows that for higher energy electrons (>400 keV), good convergence of the results is seen even within images of poor resolution. Above 400 keV, a voxel resolution as large as 300 microm results in dosimetry errors below 5%. For low-energy electrons and high-resolution images, the self-dose to marrow is also determined to within 5% accuracy. Nevertheless, increased voxelization of the image overestimates the surface area of the bone-marrow interface leading to errors in the cross-dose to bone as high as 25% for some low-energy beta emitters.

Bone Marrow↗
PubMed2006

Preparation of cyclotron-produced 186Re and comparison with reactor-produced 186Re and generator-produced 188Re for the labeling of bombesin.

The radioisotopes (186)Re and (188)Re have been extensively investigated for various forms of radiotherapy due to their useful and high-abundance beta particle emissions, low-abundance and imageable gamma-rays, and chemical resemblance to technetium. In addition, (188)Re is available in no-carrier-added (NCA) form from long lived W-188 generators, whereas (186)Re can be produced in large quantities from reactors, although not in NCA form. However, NCA (186)Re can be produced on a cyclotron by a (p,n) reaction on (186)W. The purpose of this study was to compare labeling of the peptide bombesin with these three forms of rhenium radioisotopes. Cyclotron-produced NCA (186)Re was separated radiochemically from enriched (186)W (96.9%) targets using high-purity methyl ethyl ketone (MEK). The resulting (186)Re-MEK was then loaded onto a small alumina column to separate the resulting NCA (186)Re from any remaining (186)W. The experimental levels of impurities associated with (186)Re at the end of the separation process were found to be 5.7 x 10(-6) Ci of (182)Re (0.57%, t(1/2) = 12.7 h) and 1.283 x 10(-5) Ci of (182m)Re (1.28%, t(1/2) = 2.67 days). The radionuclidic purity of the separated (186)Re was found to be 99.6%, whereas the chemical identity was determined by reversed phase high-performance liquid chromatography (RP-HPLC) to be perrhenate ((186)ReO(4)(-)). Generator-produced (188)ReO(4)(-) from a (188)W/(188)Re generator (Oak Ridge National Laboratory) and CA (186)ReO(4)(-) produced from a (185)Re(n,gamma)(186)Re reaction at the University of Missouri Research Reactor (MURR) were used for comparison with the NCA (186)Re in subsequent studies. N(3)S-5-Ava-BBN(7-14)NH(2) conjugates provide flexibility for designing (186,188)Re-labeled conjugates that retain high in vitro and in vivo specificity targeting of GRP receptor-expressing cells. This study showed that the N(3)S-5-Ava-BBN(7-14)NH(2) could be labeled with (186,188)Re following the preconjugation, postmetallation approach. The (186,188)Re(V)O-N(3)S-5-Ava-BBN(7-14)NH(2) complexes were found to form stable complexes following the reduction of perrhenate (Re(VII)O(4)(-)) with stannous chloride at room temperature, as verified by HPLC and stability studies. The radiolabeling yield was found to be >90%. The HPLC chromatograms of (186,188)Re-N(3)S-5-Ava-BBN(7-14)NH(2) complexes revealed two peaks for each conjugate, reflecting the presence of syn- and anti-isomers, which were resolvable by HPLC but re-isomerized on separation. The biodistribution studies showed that the compounds were excreted through the renal and hepatobiliary systems and demonstrated receptor-specific uptake with an average pancreas accumulation of 8.15% ID/g at 1 h postinjection. Administration of cold BBN effectively blocked pancreatic uptake and further reflects the high specificity this conjugate has for the GRP receptors. At low levels of radioactivity, radiolysis effects were not observed. Scale-up may or may not elicit this effect, particularly for the higher energy beta emitter (188)Re. The biodistribution studies demonstrated that the CA and NCA (186,188)Re conjugates behaved similarly, raising the question of whether NCA (186,188)Re is necessary for specific tumor receptor targeting.

Animals↗
PubMed1997

Physics and basic parameters of brachytherapy.

Brachytherapy (short-distance therapy) is the therapeutic process whereby radioactive sources are placed into very close proximity to target tissue. Radioactive materials were so used beginning shortly after the discovery of radium by Marie and Pierre Curie in 1898. For the purposes of brachytherapy, radioactive materials are those that emit "rays" that can cause ionization (and hence DNA damage and the destruction of target cells). The potentially useful rays include beta, gamma, and other possibilities such as neutrons. Beta rays, properly beta particles, are simply high energy electrons. Gamma rays are high energy photons (part of the electromagnetic spectrum like visible light, but with much higher energy). These particles are produced during the radioactive decay of certain isotopes. The physics of those events and the parameters that apply to the therapeutic use of the isotopes are the primary topics of this report.

Brachytherapy↗